- Identifying cases of very early (acute) hepatitis C virus infection can be difficult
- To help diagnose acute HCV, a high-tech test—polymerase chain reaction (PCR)—is necessary
- Researchers in Ontario call for rapid access to PCR testing in cases of suspected acute HCV
Acute HCV can infect the liver and cause severe inflammation of this organ. If left undiagnosed or untreated, HCV infection can become a chronic condition. Over many years, HCV causes healthy liver tissue to be replaced with useless scar tissue. As the amount of scar tissue accumulates and the liver degrades, symptoms can appear, including severe fatigue, fluid buildup in the abdomen, internal bleeding, severe abdominal infections, yellowing of the skin (jaundice), difficulty thinking clearly and memory problems. Eventually the liver can stop functioning. The accumulation of scar tissue increases the risk of liver cancer and death.
Chronic HCV can be diagnosed with blood tests. Additional blood tests and abdominal scans can reveal more about the health of the liver. Once-daily oral treatments for HCV are available in Canada and other high-income countries. These treatments are highly effective, with cure rates of 95% or greater.
The spread of HCV
Canada’s blood supply is screened, heat treated and safe. As a result, the risk of HCV, HIV and other major blood-borne germs from transfusion or use of blood products (such as clotting factor) is virtually zero. Today, the most common route for new HCV infections in Canada and other high-income countries is via the sharing of contaminated equipment for drug use.
About 20 years ago, researchers began to document another route of HCV transmission—condomless anal intercourse among gay, bisexual and other men who have sex with men (MSM). In one study, HCV was found in the semen of one-third of men who also had the virus in their blood.
Acute HCV infection
Most people who have acute (very recent) HCV infection have no symptoms or generally mild symptoms similar to a cold or flu. However, some people can develop symptoms two to 12 weeks after acute HCV has occurred, including the following:
- yellowing of the skin and/or the white part of the eye
- nausea and/or vomiting
- loss of appetite
- severe lack of energy or tiredness
- abdominal discomfort or pain
- fever
- dark urine
- light-coloured stool
These symptoms usually resolve after a few weeks.
Lab tests
Lab tests used to help diagnose HCV include an HCV antibody test. However, the immune system does not usually begin to produce high levels of antibodies until about two to three months after HCV infection has occurred. Thus, if an HCV antibody test is done during the first few weeks after infection, it is likely to be negative and may miss acute infection.
Another test that can help diagnose HCV is PCR (polymerase chain reaction). This test can detect the genetic material of the virus and measure the amount of HCV in the blood. It can also reveal the strain, or genotype, of HCV. However, access to PCR for HCV diagnosis is usually done through a two-step process. In some jurisdictions, a person first has to have a positive antibody test, indicating that exposure to HCV has occurred. Only then is PCR done to find out if HCV infection is active. This two-step process is reasonable for assessing people with chronic HCV infection. However, this algorithm can inadvertently hamper a doctor’s ability to diagnose acute HCV infection.
Acute HCV in Ontario
A team of researchers—specialists in infectious diseases and liver health—in Ontario reported difficulty in initially attempting to secure PCR testing so that they could prove that their patients had acute HCV. They warn that the “current testing [algorithm] can lead to delays in diagnosis of six months or more, as these [algorithms] do not account for time [for detectable HCV antibodies to develop].” They stated that this delay “may potentiate ongoing transmission as patients are unaware of their infection status.”
They added that their cases “emphasize the importance of assessing for acute HCV infection with PCR in patients [who have significantly elevated levels of liver enzymes in their blood],” especially if patients fit into one of the following categories:
- are sexually active MSM
- are HIV positive
- have travelled to a region where HCV is relatively common
Case details
Researchers reported details on two men who sought help at the emergency department of a hospital in Toronto.
Case 1
A man in his early 30s sought care because he was feeling extremely unwell and had yellow skin for several days. Two weeks before, he had returned to Canada from a trip to Miami, Florida. The man was HIV negative and taking pre-exposure prophylaxis (PrEP) to reduce his risk for acquiring HIV. In Miami, he had receptive condomless intercourse and oral sex with multiple partners. Three days prior to the onset of symptoms he began to take the antibiotic doxycycline to treat chlamydia infection of his urinary tract. Once his symptoms (jaundice and so on) developed, he stopped taking the antibiotic because he was concerned that it may have caused his symptoms.
Tests done at a hospital in Toronto revealed that he had extremely high levels of liver enzymes in his blood, suggestive of liver injury. Most other blood tests were within the normal range. He reported no history of alcohol or drug use. Doctors made a presumptive diagnosis of acute hepatitis. The next day he was referred to a liver specialist who said that the patient most likely had acute HCV infection. The patient tested negative for HCV antibodies, but this was not surprising, as it can take months after acute infection for such antibodies to appear.
The algorithm that Ontario’s reference laboratory follows is meant to help doctors and nurses when diagnosing chronic HCV. In such cases, people must first test positive for HCV antibodies before they can get a PCR test. Nevertheless, the researchers requested a PCR test to prove that the patient had acute HCV. The lab declined to use the test, as the patient’s blood samples had tested negative for HCV antibodies. The researchers explained their reasoning and appealed the decision. As a result, several days later, the lab performed a PCR test. The lab found that the man had a very high HCV viral load (greater than 10 million IU/mL) and his strain of HCV was genotype 1a.
Due to his severe symptoms, researchers prescribed a pill called Epclusa, which contains a combination of two potent drugs—sofosbuvir + velpatasvir. It is taken once daily with or without food. Several days after initiation of Epclusa, the man’s viral load began to fall and researchers noted that “his symptoms improved substantially.”
Case 2
A man with HIV in his early 40s was taking an HIV treatment called Triumeq (dolutegravir + abacavir + 3TC) and his HIV was suppressed. He had also recently travelled to Miami, where he engaged in condomless anal receptive sex and oral sex with multiple partners. According to the researchers, “he had used intranasally administered cocaine but gave no history of substantial alcohol use.” The researchers did note that “sharing straws for intranasal cocaine is a potential source of [HCV] infection.”
In Florida, the man developed jaundice and felt extremely unwell. He sought hospitalization, and during his hospital stay he was diagnosed with hepatitis due to elevated liver enzymes. He tested negative for antibodies to HCV, so doctors ruled this virus out as a cause of his liver injury. Instead, they diagnosed him with liver injury arising from exposure to his HIV medicines. Note that such an adverse drug reaction is very rare.
On his return to Toronto, the man visited the emergency department of a hospital. By this time his symptoms had become mild, however, liver enzyme levels in his blood were still elevated.
A week after his return to Toronto, the hospital in Miami notified him that a PCR test done while he was there was positive for HCV. Upon learning this, doctors in Toronto diagnosed him with acute HCV infection and subsequently prescribed Epclusa.
Bear in mind
In both cases, doctors who initially evaluated the men thought that acute HCV infection was unlikely because the men did not report sharing equipment for injecting drugs. However, acute HCV was diagnosed with the use of PCR.
The researchers made the following points:
“Acute HCV infection is often overlooked as a cause for acute [elevation of liver enzymes], with or without liver failure, and routine methods of testing are not sensitive for ruling out infection. The active transmission of HCV in the MSM population is globally interconnected through overlapping social networks, which poses a risk of both primary and re-infection for people who are active in these networks. As public health measures implemented during the COVID-19 pandemic are lifted and international travel rebounds, an increase in HCV cases is to be expected. In both of these cases, the patients’ risk of infection was increased by travel in early 2022 to Florida, where international social networks overlap.”
—Sean R. Hosein
Resources
Hepatitis C testing and diagnosis – CATIE
Three Canadian provinces not on track to eliminate hepatitis C by 2030 – CATIE News
Curing Hepatitis C – what you need to know – CATIE
REFERENCES:
- Wei S, Bogoch II, Dhalla IA, et al. Sexually acquired severe acute hepatitis C infection in men who have sex with men. CMAJ. 2022 Nov 21;194(45):E1537-E1540.
- Monin MB, Ingiliz P, Lutz T, et al. Low spontaneous clearance rates of recently acquired hepatitis C virus in human immunodeficiency virus-positive men who have sex with men (PROBE-C Study). Clinical Infectious Diseases. 2023 Feb 8;76(3):e607-e612.
- Bradshaw D, Lamoury F, Catlett B, et al. A comparison of seminal hepatitis C virus (HCV) RNA levels during recent and chronic HCV infection in HIV-infected and HIV-uninfected individuals. Journal of Infectious Diseases. 2015 Mar 1;211(5):736-43.
- Turner SS, Gianella S, Yip MJ, et al. Shedding of hepatitis C virus in semen of human immunodeficiency virus-infected men. Open Forum Infectious Diseases. 2016 Mar 11;3(2): ofw057.
- Li H, Marks KM, Talal AH, et al. Assessing routes of hepatitis C transmission in HIV-infected men who have sex with men using single genome sequencing. PLoS One. 2020 Jul 15;15(7):e0235237.
- Pelchen-Matthews A, Larsen JF, Shepherd L, et al. Hypersensitivity reactions, hepatotoxicity, and other discontinuations in persons receiving integrase strand transfer inhibitors: results from the EuroSIDA study. HIV Research and Clinical Practice. 2021 Dec;22(6):160-168.
- Schmidt AJ, Rockstroh JK, Vogel M, et al. Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany—a case-control study. PLoS One. 2011 Mar 8;6(3):e17781.
- van de Laar T, Pybus O, Bruisten S, et al. Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men. Gastroenterology. 2009 May;136(5):1609-17.